This application requests support for a broad analysis of the breast cancer problem. Although the principal emphasis is on the mouse and rat mammary systems, future work on the human system is also contemplated. In the rodent system we will undertake a thorough analysis of the cell populations comprising normal, preneoplastic and neoplastic mammary tissues. Strong emphasis will be given to the development of methods for distinguishing between normal, preneoplastic and neoplastic cells, for characterizing transformed cells in vitro, for devising an in vitro infectivity assay for MTV, to distinguish between hormone-dependent and -independent tumors, and for the prevention of preneoplastic transformation. The role of hormones, mammary tumor viruses, genetically determined susceptibility and resistance factors, immunologic factors, regulatory factors and a variety of non-viral oncogenic factors will be investigated. In addition, one part of our program will be devoted to analysis of oncogenic effects on mice and rats subjected perinatally to different carcinogenic and non-carcinogenic compounds and to different environmental factors. Finally, we would use the rodent model in analysis of the factors controlling carcinogenesis in the human breast. BIBLIOGRAPHIC REFERENCES: Michael T. White and S. Nandi. Biochemical studies on mitochondria isolated from normal and neoplastic tissues of the mouse mammary gland. Journal of the National Cancer Institute 56(1):65-73, 1976. C. Dickson, J.P. Puma and S. Nandi. Identification of precursor protein to the major glycoproteins of mouse mammary tumor virus. Journal of Virology 17(1):275-282, 1976.